J. Milija et al., tRNA synthetase mutants of Escherichia coli K-12 are resistant to the gyrase inhibitor novobiocin, J BACT, 181(9), 1999, pp. 2979-2983
In previous studies we demonstrated that mutations in the genes cysB, cysE,
and cls (nov) affect resistance of Escherichia coil to novobiocin (J. Rako
njac, M. Milic, and D. J. Savic, Mel. Gen. Genet. 228:307-311, 1991; R Ivan
isevic, M. Milic, D. Ajdic, J. Rakonjac, and D. J. Savic, J. Bacteriol. 177
:1766-1771, 1995). In this work we expand this list with mutations in rpoN
(the gene for RNA polymerase subunit sigma(54)) and the tRNA synthetase gen
es alaS, argS, ileS, and leuS. Similarly to resistance to the penicillin an
tibiotic mecillinam, resistance to novobiocin of tRNA synthetase mutants ap
pears to depend upon the ReIA-mediated stringent response. However, at this
point the overlapping pathways of mecillinam and novobiocin resistance div
erge. Under conditions of stringent response induction, either by the prese
nce of tRNA synthetase mutations or by constitutive production of RelA prot
ein, inactivation of the cls gene diminishes resistance to novobiocin but n
ot to mecillinam.